 |
Bacteriology at UW-Madison
|
The Microbial World
Lectures in Microbiology by Kenneth Todar PhD University of Wisconsin-Madison Department of Bacteriology
Influenza
© 2008 Kenneth Todar PhD
Influenza
Influenza viruses belong to the orthomyxoviruses,
a family of spherical or oval-shaped, enveloped (-)RNA viruses with a
segmented genome. Three types
of influenza viruses are known, Types A, B and C. All cause acute
respiratory disease in humans.
Influenza
Virus H5N1 (avian influenza)
Influenza (flu) is a short-lived fever associated with soreness and
redness of the respiratory passages and a dry cough. The virus infects
the mucous membranes of the upper respiratory tract and occasionally
invades the lungs. No diarrhea is seen in this disease, and the term
"intestinal flu" has nothing to do with the influenza viruses.
Systemic symptoms of flu include fever (101-104o/3-7 days),
shivering, chills, fatigue, headache and general aching. Recovery is
usually spontaneous and rapid. Uncomplicated influenza generally lasts
anywhere from 7 to 10 days.
The virus is transmitted through the air, primarily in droplets
expelled in coughing and sneezing.
Flu has a high mortality rate in the very young, the aged, and persons
with a lowered resistance. Death may be due to the virus itself, but
more commonly it is caused by secondary bacterial invasion resulting in
pneumonia. The
bacteria involved usually are Streptococcus
pneumoniae, Staphylococcus
aureus and Haemophilus
influenzae.
Influenza types A or B viruses cause epidemics of disease almost every
winter. In the United States, these winter influenza epidemics can
cause illness in 10 to 20% of people and are associated with an
average of 36,000 deaths and 114,000 hospitalizations per year. Getting
a flu shot can prevent illness from types A and B influenza. Influenza
type C infections cause a mild respiratory illness and are not thought
to cause epidemics. The flu vaccines do not protect against type C
influenza.
Left.
Influenza A virus illustration. Right. Influenza virus colorized
electron micrograph.
Antigenicity, Antigenic Shift and
Antigenic Drift in Influenza Viruses
The original strains of influenza viruses isolated in 1933 are referred
to as Type A or "A classic". Additional strains that have been
discovered on the basis of antigenic studies, include types A1
A2 (Asian), B and C.
Influenza type A viruses are divided into subtypes based on two
proteins on the surface of the virus. These proteins are called
hemagglutinin (H) and neuraminidase (N). There are 15
different hemagglutinin subtypes and 9 different neuraminidase
subtypes, all of which have been found among influenza A viruses in
wild birds. Wild birds are the primary natural reservoir for all
subtypes of influenza A viruses and are thought to be the source of
influenza A viruses in all other animals. Most influenza viruses cause
asymptomatic or mild infection in birds; however, the range of symptoms
in birds varies greatly depending on the strain of virus. Infection
with certain avian influenza A viruses (for example, some strains of H5
and H7 viruses) can cause widespread disease and death among some
species of wild and especially domestic birds such as chickens and
turkeys.
The current subtypes of
influenza A viruses found in people are A(H1N1) and A(H3N2). Influenza
B virus is not divided into subtypes. Influenza A(H1N1), A(H3N2), and
influenza B strains are included in each year's influenza vaccine.
The influenza virus will cause agglutination of chicken red blood
cells, a phenomenon called viral hemagglutination. In fact, the
hemagglutinating ability of a diluted suspension of viruses can be
used to measure the concentration of the viruses. The
hemagglutinating ability is inhibited by antibody specific for the
antigenic subgroup of the virus. The virus is capable of agglutinating
red blood cells because it contains a specific protein - the hemagglutinin spike - on its
envelope, which attaches to a specific receptor site in the chicken rbc.
The virus also possesses an enzyme, neuraminidase,
that destroys the
receptor sites on chicken erythrocytes. The enzyme is antigenically
distinct from the hemagglutinin but also exists as a glycoprotein
"spike" in the
lipoidal envelope. If rbc's are incubated in the presence of virus
particles, they will rapidly agglutinate, but as they continue to
incubate, neuraminidase will destroy the rbc receptor and release the
virus.
The hemagglutinin and neuraminidase spikes of the virus constitute
the H and N antigens. Thus, the specific serotype of an influenza virus
may be expressed as A(H1N1) or A(H3N2), and so on. The H and N antigens
are essential for the virulence of the virus: the H antigen is involved
in attachment and the N antigen is probably involved in penetration and
the eventual release of
the virus. Both the H and N antigens of the virus are recognized by the
immune mechanisms of the host and antibody raised against these
antigens either by infection or vaccination is protective.
Influenza viruses display a genetic
plasticity that is unique among
disease-producing viruses. Their genome exists as 8 discrete pieces of
RNA. Each piece is an intact gene that encodes at least one
characteristic of the virus. Genetic plasticity arises from the
ease with which these genes are interchanged among different strains.
If a host cell is simultaneously infected by two different strains of
of influenza virus, the genes from these strains can undergo a random
reassortment in the cell to produce one or more hybrid strains, which
differ in the exact nature of antigens on their surface. This so-called
antigenic shift enables the new
hybrid
virus to bypass any immunity to the parent strains which has built up
in the
population, thereby rendering that population once more susceptible
to infection and making possible the initiation of epidemics.
Another way that influenza viruses can change is is called antigenic drift. These are small
changes in the virus that happen continually over time. Antigenic drift
also produces new virus strains that may not be recognized by the
body's immune system. A person infected with a particular flu virus
strain develops antibody against that virus. As newer virus strains
appear, displaying new antigens, the antibodies against the older
strains no longer recognize
the "newer" virus, which allows reinfection to occur. This is one of
the main
reasons why people can get the flu more than one time. In most years,
one or two of the three virus strains in the influenza vaccine are
updated to keep up with the changes in the prevailing flu viruses.
Therefore, those who want to be protected from flu need to get a flu
shot every
year.
Antigenic shift is an abrupt, major change in the influenza A viruses,
resulting in new hemagglutinin and/or new neuraminidase proteins
in influenza viruses that infect humans. Shift
results in a new influenza A subtype. When shift happens, most people
have little or no protection against the new virus. While influenza
viruses are changing by antigenic drift all the time, antigenic shift
happens only occasionally. Type A viruses undergo both kinds of
changes; influenza type B viruses change only by the more gradual
process of antigenic drift.
Influenza Epidemiology
Localized epidemics of influenza occur every 2-3 years. Several
world-wide pandemics have occurred in the last 400 years, the most
disastrous of record being the 1918-1919 pandemic of "Spanish Flu",
which killed 20 million
world-wide and 500,000 in the U.S. These pandemics occur every 10-40
years.
The 1957 outbreak of the so called "Asian flu" provided an opportunity
to study influenza in its pandemic form. The pandemic arose when a
new virus strain, differing antigenically from all previous strains,
appeared in the population. Since immunity to this strain was not
present, the virus was able to spread rapidly throughout the world. The
original epidemic first appeared in the interior of China, from where
it spread to Hong Kong, then was spread by naval ships to San Diego and
Newport, Rhode Island. After reaching the U.S. in this fashion,
outbreaks continuously occurred in various parts of the country,
eventually accounting for 22 million new cases of flu.
Evidence links the pandemics of 1918 and 1957 to the reassortment of
avian influenza viral genes and human influenza viral genes in swine.
Pigs can be infected with swine, human and/or avian
strains at the same time, allowing two unrelated viruses to undergo a
genetic reassortment of their RNA segments (antigenic shift), leading
to the
emergence of a new strain that will infect humans and for which there
is no preexisting immunity in members of the population.
A new avian influenza strain
appeared in Hong Hong in 1997, apparently jumping directly from the
avian host to humans. The resulting strain A(H5N1), also called avian influenza virus, infected 18
people in Hong Kong and caused 6 deaths. Since
2003, more than 100 human H5N1 cases have been diagnosed in Thailand,
Vietnam, Cambodia, and Indonesia. Of those cases, more than half have
died as a result of the virus. Close contact with infected poultry has
been the primary source for human infection. Though rare, there have
been isolated reports of human-to-human transmission of the virus.
Genetic studies confirm that the influenza A virus
H5N1 mutates rapidly. Should it adapt to allow easy human-to-human
transmission, a pandemic could ensue. At this time, it is uncertain
whether the currently
circulating H5N1 virus will lead to a global disease outbreak in humans.
Vaccines to protect humans against H5N1 viruses are
currently under development. In addition, research is underway on
methods to rapidly produce
large quantities of vaccine. So far, research suggests that two
antiviral
medicines, oseltamavir (Tamiflu®) and zanamavir (Relenza®), may
be
useful treatments for H5N1 avian influenza. However, H5N1 viruses are
generally resistant to two other available antiviral medications,
amantadine and rimantadine, so they cannot be used to treat avian flu.
Treatment of Influenza
Uncomplicated influenza is treated similar to the common cold. Although
antibiotics are often prescribed, they have no effect on the virus but
may prevent
or cure bacterial superinfection. The drug amantadine may
prevent
influenza if taken continuously by high-risk persons at the time of an
epidemic,
but is not used widely. Two antiviral
medicines, oseltamavir (Tamiflu®) and zanamavir (Relenza®), may
be
useful in the treatment of avian flu. However, H5N1 avian flu viruses
are
generally resistant to
amantadine and rimantadine.
Immunity to Influenza
Persons recovering from natural infection acquire some resistance to
reinfection with the particular antigenic strain. But new strains
possessing new minor antigens develop and consequently cause successive
attacks of influenza.
Vaccines
The single best way to prevent the flu is to get a flu vaccination each
fall. There are two types of vaccines available in the U.S.:
1. The "flu shot" – an inactivated vaccine (containing 'killed' virus)
that is given with a needle. The flu shot is approved
for use in people older than 6 months, whether healthy or with chronic
medical conditions.
2. The nasal-spray flu vaccine
– a vaccine made with live, weakened flu
viruses that do not cause the flu (sometimes called LAIV for “Live
Attenuated Influenza Vaccine”). LAIV is approved for use in healthy
people 5 years to 49 years of age who are not pregnant. About
two weeks after vaccination, antibodies develop that protect against
influenza virus infection. Flu vaccines will not protect against
influenza-like illnesses caused by other viruses.
October
or November is the best time to get vaccinated, but getting vaccinated
in December or even later can still be beneficial. Flu season can begin
as early as October and last as late as May.
In
general, anyone who wants to reduce their chances of getting the flu
can get vaccinated. However, certain people should get vaccinated each
year. They are either people who are at high risk of having serious flu
complications or people who live with or care for those at high risk
for serious complications.
CDC recommends that the following people
should be vaccinated each year.
- People 65 years and older.
- People who live in nursing homes and other long-term care facilities
that house those with long-term illnesses
- Adults and children 6 months and older with chronic heart or lung
conditions, including asthma.
- Adults
and children 6 months and older who needed regular medical care or were
in a hospital during the previous year because of a metabolic disease
(like diabetes), chronic kidney disease, or weakened immune system
(including immune system problems caused by medicines or by infection
with human immunodeficiency virus [HIV/AIDS]).
- Children
6 months to 18 years of age who are on long-term aspirin therapy.
(Children given aspirin while they have influenza are at risk of Reye
syndrome.)
- Women who will be pregnant during the influenza season.
- All children 6 to 23 months of age.
- People
with any condition that can compromise respiratory function or the
handling of respiratory secretions (that is, a condition that makes it
hard to breathe or swallow, such as brain injury or disease, spinal
cord injuries, seizure disorders, or other nerve or muscle disorders.)
- People 50 to 64 years of age who
have one or more medical conditions that place them at increased risk
for serious flu complications.
- Any person in close contact with someone in
a high-risk group (see
above). This includes all health-care workers,
household contacts and out-of-home caregivers of children 6 to 23
months of age, and close contacts of people 65 years and older.
People who should not be vaccinated without
first consulting a physician include:
- People who have a severe allergy to chicken eggs.
- People who have had a severe reaction to an influenza vaccination in
the past.
- People who developed Guillain-Barre syndrome within 6 weeks of
getting an influenza vaccine previously.
- Children less than 6 months of age (influenza vaccine is not approved
for use in this age group).
- People who have a moderate or severe illness with a fever should wait
to get vaccinated until their symptoms lessen.
Influenza Websites
CDC: Avian
Influenza
Infections in Humans
CDC: Influenza (Flu).
CDC: The
Influenza Viruses
Stanford: The
Influenza pandemic of 1918
University
of Capetown: Influenza
University of
Maryland: Avian Influenza Virus Program
WHO: Avian
Influenza
Written and Edited by Kenneth Todar. All rights
reserved.
Return to The Microbial World Homepage